The present invention relates to an oral composition comprising an active extract of certain species of the genus Dioscorea, in particular to an oral composition capable of enhancing the proliferation and differentiation of cells, and of alleviating the side effects induced by chemotherapy. The present invention provides a method for treatment of osteoporosis and a method for alleviation of side effects caused by chemotherapy.
Plants of the genus Dioscorea, also known as “wild yam,” are members of the monocotyledonous family Dioscoreaceae, which is distributed in the tropical and subtropical regions. There are about 650 species in the world, of which 93 species and 9 varieties are found in China, and 14 species and 5 varieties are found in Taiwan.
Dioscorea is one of the very important pharmaceutical plants used in traditional Chinese medicine, and the medicinal effects thereof have been studied for years. In 1936, Tsukamoto et al isolated diosgenin, a steroid saponin of Dioscorea, from Dioscoreacea family of plants and then use it as raw material for rapid synthesis of medicinal steroids. In Aradhana, M., Rao, A. C. and Kale, R. K., Indian Journal of Experimental Biology 30:367-370, 1992, it was indicated that diosgenin promotes the growth of epithelial cells of rat mammary glands. Beneytout, J. L., et al., Biochemical & Biophysical Research Communications 207(1):398-404, February 1995, reported that diosgenin induces morphological and biochemical changes characteristic of megakaryocyte cells when diosgenin is added to human erythroleukemia (HEL) cell cultures and, thus, diosgenin can be used as a megakaryotic differentiation inducer of HEL cells. In Araghiniknam, M., et al., Life Sciences 59(11):147-157, 1996, a steroid extract of Dioscorea was indicated to possess significant activities as an anti-oxidant to modify serum lipid levels.
Dehydroepiandrosterone (DHEA) has a similar chemical structure to diosgenin, and is known to have anti-cancer, anti-oxidation, and anti-diabetic effects, as well as an effect on the regulation of bone mass. The serum levels of DHEA gradually decrease as age increases, and are related to aging. It was speculated from various studies that the diosgenin extract of Dioscorea might be converted into DHEA in the human body and thus supplements the DHEA which decreases with aging. However, these studies were only conducted on old people taking diosgenin present in the Dioscorea to investigate if diosgenin could reduce the over-oxidation of serum lipids, lower the triglycerides in blood serum and increase high density level (HDL) of cholesterol while decreasing the over-oxidation damage of low density level (LDL) of cholesterol.
Concerning the effect of DHEA on regulation of bone mass, Scheven, B. A. A., et al., Life Science 62(1):59-68, 1998, reported that DHEA and its sulfate derivative (DHEA-S) failed on their own to exert direct, independent, significant effects on the growth and differentiation of human osteoblastic cells, but treating the cells in conjunction with a bone cell modulating agent, 1,25-dihydroxyvitamin D3, (1,25(OH)2D3), resulted in enhancement of specific alkaline phosphatase (ALP) activity, which is the specific marker of maturing osteoblastic cells. This study shows that the effects of DHEA and DHEA-S on osteoblastic cell growth and differentiation are likely to be mediated via an effect on 1,25(OH)2D3-induced change in bone cells.
In accordance with the present invention, it was found that the extract of a particular Dioscorea species harvested from the Yang-Ming Mountain in Taiwan, R.O.C., Dioscorea alata L. cv. Phyto, which has been given the scientific name “Dioscorea alata (No. YMM-PH3)” by the Research Center for Drug Discovery at the National Yang Ming University, Taipei, Taiwan, R.O.C., (referred to hereinafter as “Dioscorea alata L. cv. Phyto”), and further extracted fractions possess biological activity on cell regeneration.
Specifically, it was found that the extract of the Dioscorea alata L. cv. Phyto and the further extracted fractions per se, and it is believed that extracts of other Dioscorea species, generally referred to herein with Dioscorea alata L. cv. Phyto together as “Dioscorea sp.” unless otherwise clear from the context, without the presence of any bone cell modulating agent, can stimulate the proliferation and differentiation of the osteoprogenitor cells so as to supplement the osteoprogenitor cells in the bone and promote maturity of osteoblastic cells and mineralization of osteoblastic cells, thereby achieving bone repair, restoration and reproduction and in turn preventing and treating osteoporosis. Moreover, the extract of the Dioscorea alata L. cv. Phyto, and, it is believed, other Dioscorea sp., not only stimulates the proliferation and differentiation of hematopoietic stem cells in bone marrow in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), but also facilitates recovery of patients suffering from the deficiency of leukocytes and erythrocytes caused by anti-cancer drug treatment, and thus, can be used in combination with an anti-cancer drug as a chemotherapeutic adjuvant.